4-Fluorobenzylamine → (2S)-ethyl 2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-2-((4-fluorobenzyl)carbamoyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

Participants

Reaction Steps

To a mixture of 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acid (21 mg, 0.042 mmol) and (4-fluorophenyl)methanamine (10.52 mg, 0.084 mmol) in DMF (1 mL) was added DIEA (0.037 mL, 0.210 mmol), HATU (32.0 mg, 0.084 mmol) and DMAP (1.027 mg, 8.41 μmol) and the resulting mixture was stirred at rt for 16 h. At this point LCMS indicated completion of reaction. The reaction mixture was then filtered and purified by prep HPLC to afford (2S)-ethyl 2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-2-((4-fluorobenzyl)carbamoyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (12 mg, 0.020 mmol, 47.1% yield) as off-white solid. 1H NMR (500 MHz, CDCl3) δ: 7.34-7.30 (m, 2H), 7.23 (t, J=6.4 Hz, 1H), 7.20 (s, 1H), 7.06-6.99 (m, 2H), 6.85 (d, J=10.7 Hz, 1H), 4.96 (s, 1H), 4.67-4.53 (m, 2H), 4.35 (t, J=5.3 Hz, 2H), 4.15 (q, J=7.0 Hz, 2H), 2.79 (s, 3H), 2.76 (t, J=6.6 Hz, 2H), 2.24-2.14 (m, 2H), 1.82 (s, 3H), 1.21 (t, J=7.2 Hz, 3H), 1.17 (s, 9H). LCMS (M+H)=607.4.

Provenance & Evidence